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1.
Nature ; 606(7916): 937-944, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35676482

RESUMO

During infection, animals exhibit adaptive changes in physiology and behaviour aimed at increasing survival. Although many causes of infection exist, they trigger similar stereotyped symptoms such as fever, warmth-seeking, loss of appetite and fatigue1,2. Yet exactly how the nervous system alters body temperature and triggers sickness behaviours to coordinate responses to infection remains unknown. Here we identify a previously uncharacterized population of neurons in the ventral medial preoptic area (VMPO) of the hypothalamus that are activated after sickness induced by lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid. These neurons are crucial for generating a fever response and other sickness symptoms such as warmth-seeking and loss of appetite. Single-nucleus RNA-sequencing and multiplexed error-robust fluorescence in situ hybridization uncovered the identity and distribution of LPS-activated VMPO (VMPOLPS) neurons and non-neuronal cells. Gene expression and electrophysiological measurements implicate a paracrine mechanism in which the release of immune signals by non-neuronal cells during infection activates nearby VMPOLPS neurons. Finally, we show that VMPOLPS neurons exert a broad influence on the activity of brain areas associated with behavioural and homeostatic functions and are synaptically and functionally connected to circuit nodes controlling body temperature and appetite. Together, these results uncover VMPOLPS neurons as a control hub that integrates immune signals to orchestrate multiple sickness symptoms in response to infection.


Assuntos
Apetite , Febre , Infecções , Neurônios , Área Pré-Óptica , Animais , Apetite/efeitos dos fármacos , Depressores do Apetite/farmacologia , Febre/induzido quimicamente , Febre/fisiopatologia , Hibridização in Situ Fluorescente , Infecções/induzido quimicamente , Infecções/fisiopatologia , Lipopolissacarídeos , Neurônios/efeitos dos fármacos , Comunicação Parácrina , Poli I-C , Área Pré-Óptica/citologia , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/fisiologia
2.
Chest ; 161(1): e35-e41, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35000715

RESUMO

CASE PRESENTATION: A 71-year-old man with history of gastroesophageal reflux disease, chronic sinusitis, arthritis, hypothyroidism, and anemia of chronic disease initially sought treatment with a recurrent left pleural effusion along with other abnormal lung findings on chest CT scan. Before his referral, he was being managed for 3 years at his local hospital for waxing and waning fevers, fatigue, productive cough, chills, and night sweats. He did not report any hemoptysis or chest pain, but reported weight loss of 13 kgs in 15 months. During those 3 years, he was treated with multiple courses of antibiotics and steroids with temporary relief of symptoms. At that time, his chronic sinusitis was suspected to be the cause of his symptoms and he underwent balloon sinuplasty. He was receiving daily sublingual immunotherapy for inhaled respiratory allergens for the previous year after showing positive test results for 17 inhaled allergens. The patient had no other known immunologic workup before our evaluation.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pulmão/diagnóstico por imagem , Granulomatose Linfomatoide/diagnóstico , Idoso , Broncoscopia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Empiema/fisiopatologia , Infecções por Vírus Epstein-Barr , Febre/fisiopatologia , Humanos , Leucocitose/fisiopatologia , Pulmão/patologia , Granulomatose Linfomatoide/tratamento farmacológico , Granulomatose Linfomatoide/fisiopatologia , Granulomatose Linfomatoide/virologia , Masculino , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Tomografia Computadorizada por Raios X , Vincristina/uso terapêutico
3.
Comput Math Methods Med ; 2022: 2658095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35082912

RESUMO

BACKGROUND: Fever is one of the frequently occurring diseases in human beings, and the body is said to have befallen in fever if the arterial or internal body temperature rises to 38°C. The patient who suffers from fever is either given paracetamol or tepid sponging or both. OBJECTIVE: This paper is aimed at studying the effects of the tepid sponge in normalizing the high temperature of the human body during fever. Among the various available methods for tepid sponging, the impact of holding a cool wet cloth on the forehead for reducing the fever is analyzed and pictured graphically. METHOD: For analyzing the effects of tepid sponge on the temperature distribution of the domain consisting of scalp, skull, and cerebrospinal fluid (CSF), a cool wet cloth is brought in contact with the skin allowing the heat to transfer from the brain to the wet cloth through these layers. The heat transfer in living biological tissues is different from ordinary heat transfer in other nonliving materials. Therefore, a model based on the bioheat equation has been constructed. The model has been solved by numerical methods for both steady- and unsteady-state cases. The domain, which consists of the scalp, skull, and CSF layers of the human head, has been discretized into four equal parts along the axes of the three-dimensional coordinate system. The forward difference and forward time centered space approximations were employed for numerical temperature distribution results at the nodal points. RESULTS: The effects of tepid sponge in reducing the body temperature with fever at 38°C, 39.5°C, and 41°C have been numerically calculated, and the results were pictured graphically. For transient cases, the corresponding calculations have been carried out at times t = 2 minutes, 4 minutes, and 6 minutes. CONCLUSION: Among all the available remedies to fever, tepid sponging has shown a significant effect in controlling fever.


Assuntos
Encéfalo/fisiopatologia , Febre/terapia , Modelos Neurológicos , Temperatura Corporal/fisiologia , Biologia Computacional , Simulação por Computador , Febre/líquido cefalorraquidiano , Febre/fisiopatologia , Humanos , Hidroterapia/métodos , Couro Cabeludo/fisiopatologia , Crânio/fisiopatologia , Têxteis
4.
J Clin Lab Anal ; 36(1): e24050, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34786765

RESUMO

BACKGROUND: Maternal intrapartum fever has a serious impact on mother and child. However, the corresponding study seems to be in short. METHODS: The role of inflammatory cells in patients who were diagnosed with intrapartum fever lived in part of Eastern China was evaluated. The obstetrics outcomes, complete blood cell count (CBC) and thereby converted neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, monocyte to lymphocyte ratio (MLR), and vaginal secretion were compared in different groups. RESULTS: Prepartum values of white blood cell (WBC), red blood cell (RBC), and hemoglobin (Hb) were all a little higher in the febrile group than in the afebrile group, and postpartum WBC in the afebrile group was still higher while postpartum RBC and Hb were inferior to non-fever maternity. Postpartum NLR and MLR were all higher in the fever group but not preferred overtly difference before delivery. Additionally, the comparison of WBC, RBC, Hb, platelets, neutrophils, and monocytes in prepartum and postpartum all showed significant differences. CONCLUSION: The parturition could bring about the value change of CBC and intrapartum fever might aggravate or alleviate this change. Besides, the intrapartum fever might not be caused mainly by infection and the difference between bacteria and fungus could reflect in the CBC.


Assuntos
Febre , Período Periparto/fisiologia , Complicações na Gravidez , Adulto , Contagem de Células Sanguíneas , China/epidemiologia , Estudos Transversais , Feminino , Febre/epidemiologia , Febre/fisiopatologia , Humanos , Recém-Nascido , Parto , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez/epidemiologia
5.
Am J Trop Med Hyg ; 106(2): 623-625, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34844205

RESUMO

Epstein-Barr virus (EBV) is the most common cause of infectious mononucleosis (IM) and IM is a clinical syndrome typically characterized by fever, pharyngitis, and cervical lymph node enlargement. We describe the case of a 19-year-old man with IM complicated by splenic infarction. The patient visited our hospital because of upper abdominal pain without a fever and sore throat. Abdominal computed tomography revealed a low-density area in the spleen, which indicated splenic infarction. The next day, he developed a fever. After diminishing abdominal pain and fever, he developed pharyngitis accompanied by fever. Acute EBV infection was confirmed by serological tests. The patient was successfully managed with no specific therapy. Splenic infarction is a rare complication of IM and this case showed that splenic infarction can precede a fever and pharyngitis.


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Mononucleose Infecciosa/patologia , Baço/patologia , Infarto do Baço/patologia , Dor Abdominal/fisiopatologia , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Infecções por Vírus Epstein-Barr/virologia , Febre/fisiopatologia , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/patogenicidade , Humanos , Mononucleose Infecciosa/diagnóstico por imagem , Mononucleose Infecciosa/virologia , Linfadenopatia/fisiopatologia , Masculino , Faringite/fisiopatologia , Remissão Espontânea , Baço/diagnóstico por imagem , Baço/virologia , Infarto do Baço/diagnóstico por imagem , Infarto do Baço/virologia , Tomografia Computadorizada por Raios X , Adulto Jovem
6.
Medicine (Baltimore) ; 100(37): e27129, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34664837

RESUMO

ABSTRACT: The purpose of this study is to demonstrate the relationship between acute repetitive seizures and claustrum damage, and to provide basis for the treatment of repetitive seizures exclusively involved the bilateral claustrum.Between August 2014 and October 2015, 5 patients with repetitive seizures after a febrile period were admitted to our hospital, showing exclusive involvement of bilateral claustrum on magnetic resonance images (MRI). All patients underwent serum virology testing, autoimmune antibody test, MRI, and electroencephalograph examination.All patients were young women (16-29 years) with an unremarkable previous medical history, and 2 of them were pregnant. Similar clinical symptoms like antecedent febrile illness in the 3 to 7 days preceding seizures, psychiatric disorder, or dysautonomia occurred in 5 patients. Abnormal MRI signals exclusively confined to the bilateral claustrum appeared in 4 patients during the acute phase and in 1 patient during the chronic phase. All patients accepted empirical treatment with anti-viral and anti-seizure drugs and had good outcomes (seizure-free, though with some residual short-term memory loss) at the 3rd year follow-up.Although the clinical and associated brain imaging findings were characteristic, the etiology was still unclear. Contrary to previous studies, the patients presented here have all received a good prognosis.


Assuntos
Claustrum/anormalidades , Febre/complicações , Convulsões/etiologia , Adolescente , Adulto , Claustrum/diagnóstico por imagem , Feminino , Febre/fisiopatologia , Humanos , Estudos Retrospectivos , Convulsões/fisiopatologia
7.
Commun Biol ; 4(1): 984, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34413459

RESUMO

Antibody-mediated opsonic phagocytosis (OP) of Plasmodium falciparum blood-stage merozoites has been associated with protection against malaria. However, the precise contribution of different peripheral blood phagocytes in the OP mechanism remains unknown. Here, we developed an in vitro OP assay using peripheral blood leukocytes that allowed us to quantify the contribution of each phagocytic cell type in the OP of merozoites. We found that CD14 + +CD16- monocytes were the dominant phagocytic cells at very low antibody levels and Fc gamma receptor (FcγR) IIA plays a key role. At higher antibody levels however, neutrophils were the main phagocytes in the OP of merozoites with FcγRIIIB acting synergistically with FcγRIIA in the process. We found that OP activity by neutrophils was strongly associated with protection against febrile malaria in longitudinal cohort studies performed in Ghana and India. Our results demonstrate that peripheral blood neutrophils are the main phagocytes of P. falciparum blood-stage merozoites.


Assuntos
Febre/fisiopatologia , Malária Falciparum/fisiopatologia , Merozoítos/fisiologia , Neutrófilos/fisiologia , Fagocitose , Plasmodium falciparum/fisiologia , Febre/parasitologia , Malária Falciparum/parasitologia
8.
PLoS One ; 16(7): e0255141, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34297774

RESUMO

The natural history of COVID-19 and predictors of mortality in older adults need to be investigated to inform clinical operations and healthcare policy planning. A retrospective study took place in 80 long-term nursing homes in Catalonia, Spain collecting data from March 1st to May 31st, 2020. Demographic and clinical data from 2,092 RT-PCR confirmed cases of SARS-CoV-2 infection were registered, including structural characteristics of the facilities. Descriptive statistics to describe the demographic, clinical, and molecular characteristics of our sample were prepared, both overall and by their symptomatology was performed and an analysis of statistically significant bivariate differences and constructions of a logistic regression model were carried out to assess the relationship between variables. The incidence of the infection was 28%. 71% of the residents showed symptoms. Five major symptoms included: fever, dyspnea, dry cough, asthenia and diarrhea. Fever and dyspnea were by far the most frequent (50% and 28%, respectively). The presentation was predominantly acute and symptomatology persisted from days to weeks (mean 9.1 days, SD = 10,9). 16% of residents had confirmed pneumonia and 22% required hospitalization. The accumulated mortality rate was 21.75% (86% concentrated during the first 28 days at onset). A multivariate logistic regression analysis showed a positive predictive value for mortality for some variables such as age, pneumonia, fever, dyspnea, stupor refusal to oral intake and dementia (p<0.01 for all variables). Results suggest that density in the nursing homes did not account for differences in the incidence of the infection within the facilities. This study provides insights into the natural history of the disease in older adults with high dependency living in long-term nursing homes during the first pandemic wave of March-May 2020 in the region of Catalonia, and suggests that some comorbidities and symptoms have a strong predictive value for mortality.


Assuntos
COVID-19 , Dispneia , Febre , Casas de Saúde , SARS-CoV-2 , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/patologia , COVID-19/fisiopatologia , Comorbidade , Dispneia/mortalidade , Dispneia/patologia , Dispneia/fisiopatologia , Feminino , Febre/mortalidade , Febre/patologia , Febre/fisiopatologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Espanha/epidemiologia
10.
Am J Trop Med Hyg ; 105(3): 794-800, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252051

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease worldwide. It can be transmitted from person to person, and the fatality rate is very high. During this study, three SFTS clusters including 12 associated cases were identified in three counties in Zhejiang Province from 2018 to 2020. The median age of the three index patients was 70 years, and that of secondary case patients was 59 years. Of note, the mortality rate of the index patients was 100%. The mortality rate of secondary case patients was 11%. The total secondary attack rate (SAR) was 30% (9/30). The SARs of cluster A, cluster B, and cluster C were 38% (3/8), 21% (3/14), and 38% (3/8), respectively. Additionally, the interval from onset to diagnosis was 4 days. The intervals from disease onset to confirmation of the index cases and secondary cases were 7 days and 4 days, respectively. All secondary case patients had a history of close contact with blood or body fluids of the index patients. These results indicate that SFTS patients should not be discharged until recovery. When SFTS patients die, the corpses should be transferred directly from the hospital to the crematorium for cremation by persons wearing proper protective equipment to prevent virus transmission.


Assuntos
Hotspot de Doença , Febre Grave com Síndrome de Trombocitopenia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Calafrios/fisiopatologia , China/epidemiologia , Diarreia/fisiopatologia , Fadiga/fisiopatologia , Feminino , Febre/fisiopatologia , Cefaleia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Febre Grave com Síndrome de Trombocitopenia/fisiopatologia , Febre Grave com Síndrome de Trombocitopenia/transmissão , Adulto Jovem
11.
BMC Pregnancy Childbirth ; 21(1): 505, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253173

RESUMO

BACKGROUND: Evidence on the outcome of SARS-CoV-2 infection in pregnancy is generally reassuring but yet not definitive. METHODS: To specifically assess the impact of SARS-CoV-2 infection in late pregnancy, we prospectively recruited 315 consecutive women delivering in a referral hospital located in Lombardy, Italy in the early phase of the epidemic. Restriction of the recruitment to this peculiar historical time period allowed to exclude infections occurring early in pregnancy and to limit the recall bias. All recruited subjects underwent a nasopharyngeal swab to assess the presence of Sars-Cov-2 using Real-time PCR. In addition, two different types of antibodies for the virus were evaluated in peripheral blood, those against the spike proteins S1 and S2 of the envelope and those against the nucleoprotein of the nucleocapsid. Women were considered to have had SARS-CoV-2 infection in pregnancy if at least one of the three assessments was positive. RESULTS: Overall, 28 women had a diagnosis of SARS-CoV-2 infection in pregnancy (8.9%). Women diagnosed with the infection were more likely to report one or more episodes of symptoms suggestive for Covid-19 (n = 11, 39.3%) compared to unaffected women (n = 39, 13.6%). The corresponding OR was 4.11 (95%CI: 1.79-9.44). Symptoms significantly associated with Covid-19 in pregnancy included fever, cough, dyspnea and anosmia. Only one woman necessitated intensive care. Pregnancy outcome in women with and without SARS-CoV-2 infection did not also differ. CONCLUSIONS: SARS-CoV-2 infection is asymptomatic in three out of five women in late pregnancy and is rarely severe. In addition, pregnancy outcome may not be markedly affected.


Assuntos
COVID-19/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , Anosmia/fisiopatologia , Infecções Assintomáticas , COVID-19/fisiopatologia , Teste de Ácido Nucleico para COVID-19 , Teste Sorológico para COVID-19 , Tosse/fisiopatologia , Dispneia/fisiopatologia , Feminino , Febre/fisiopatologia , Humanos , Itália/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Resultado da Gravidez , Terceiro Trimestre da Gravidez , Prevalência , SARS-CoV-2 , Adulto Jovem
12.
PLoS One ; 16(7): e0254999, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34310646

RESUMO

Over the past few months, the spread of the current COVID-19 epidemic has caused tremendous damage worldwide, and unstable many countries economically. Detailed scientific analysis of this event is currently underway to come. However, it is very important to have the right facts and figures to take all possible actions that are needed to avoid COVID-19. In the practice and application of big data sciences, it is always of interest to provide the best description of the data under consideration. The recent studies have shown the potential of statistical distributions in modeling data in applied sciences, especially in medical science. In this article, we continue to carry this area of research, and introduce a new statistical model called the arcsine modified Weibull distribution. The proposed model is introduced using the modified Weibull distribution with the arcsine-X approach which is based on the trigonometric strategy. The maximum likelihood estimators of the parameters of the new model are obtained and the performance these estimators are assessed by conducting a Monte Carlo simulation study. Finally, the effectiveness and utility of the arcsine modified Weibull distribution are demonstrated by modeling COVID-19 patients data. The data set represents the survival times of fifty-three patients taken from a hospital in China. The practical application shows that the proposed model out-classed the competitive models and can be chosen as a good candidate distribution for modeling COVID-19, and other related data sets.


Assuntos
COVID-19/epidemiologia , COVID-19/mortalidade , Modelos Estatísticos , Pandemias , SARS-CoV-2/patogenicidade , COVID-19/diagnóstico , COVID-19/fisiopatologia , China/epidemiologia , Tosse/diagnóstico , Tosse/fisiopatologia , Fadiga/diagnóstico , Fadiga/fisiopatologia , Febre/diagnóstico , Febre/fisiopatologia , Hospitais , Humanos , Método de Monte Carlo , Análise de Sobrevida
14.
Med Intensiva (Engl Ed) ; 45(6): 362-370, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34103248

RESUMO

In 1348, a pandemic known as Black Death devastated humanity and changed social, economic and geopolitical world order, as is the current case with SARS-CoV-2 coronavirus. The doctor of the Nasrid Kingdom of Granada, Ibn-Jatima from Almeria, wrote "Treatise on the Plague", in which it may be found epidemiological and clinical similarities between both plagues. In the context of Greco-Arab medicine, he discovered respiratory and contact contagion of Pestis and attributed its physiopathology to a lack of pulmonary cooling of the innate heat, generated in the heart and carried by the blood humor. The process described was equivalent to the oxygen transport system. Furthermore, it was supposed to generate toxic residues, such as free radicals, leading to an irreversible multiple organ failure (MOF), considered a mortality factor as in Covid-19. Due to its similitude, it would be the first antecedent of the MOF physiopathological concept, a finding that enriches the scientific and historical heritage of our clinical specialty.


Assuntos
Medicina Arábica/história , Insuficiência de Múltiplos Órgãos/história , Pandemias/história , Peste/história , COVID-19/complicações , COVID-19/fisiopatologia , Fenômenos Fisiológicos Cardiovasculares , Febre/fisiopatologia , História Medieval , Humanos , Inflamação/fisiopatologia , Modelos Biológicos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/fisiopatologia , Flebotomia/história , Peste/complicações , Peste/fisiopatologia , Peste/terapia , Fenômenos Fisiológicos Respiratórios , SARS-CoV-2 , Mudança Social , Espanha
15.
Medicine (Baltimore) ; 100(19): e25917, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106657

RESUMO

ABSTRACT: The coronavirus disease (COVID-19) has become a global pandemic. Invasive mechanical ventilation is recommended for the management of patients with COVID-19 who have severe respiratory symptoms. However, various complications can develop after its use. The efficient and appropriate management of patients requires the identification of factors associated with an aggravation of COVID-19 respiratory symptoms to a degree where invasive mechanical ventilation becomes necessary, thereby enabling clinicians to prevent such ventilation. This retrospective study included 138 inpatients with COVID-19 at a tertiary hospital. We evaluated the differences in the demographic and clinical data between 27 patients who required invasive mechanical ventilation and 111 patients who did not. Multivariate logistic regression analysis indicated that the duration of fever, national early warning score (NEWS), and lactate dehydrogenase (LDH) levels on admission were significantly associated with invasive mechanical ventilation in this cohort. The optimal cut-off values were: fever duration ≥1 day (sensitivity 100.0%, specificity 54.95%), NEWS ≥7 (sensitivity 72.73%, specificity 92.52%), and LDH >810 mg/dL (sensitivity 56.0%, specificity 90.29%). These findings can assist in the early identification of patients who will require invasive mechanical ventilation. Further studies in larger patient populations are recommended to validate our findings.


Assuntos
COVID-19/fisiopatologia , Escore de Alerta Precoce , Respiração Artificial/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Feminino , Febre/fisiopatologia , Humanos , Hidroxicloroquina/uso terapêutico , L-Lactato Desidrogenase/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pandemias , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , SARS-CoV-2 , Fatores Sexuais , Fatores Socioeconômicos , Centros de Atenção Terciária , Adulto Jovem
16.
Eur J Clin Invest ; 51(11): e13602, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34050527

RESUMO

BACKGROUND: Currently, we remain uncertain about which patients are at increased risk for recurrent pericarditis. We developed a risk score for pericarditis recurrence in patients with acute pericarditis. MATERIALS AND METHODS: We prospectively recruited 262 patients with a first episode of acute pericarditis. Baseline patients' demographics, clinical, imaging and laboratory data were collected. Patients were followed up for a median of 51 months (interquartile range 21-71) for recurrence. Variables with <10% missingness were entered into multivariable logistic regression models with stepwise elimination to explore independent predictors of recurrence. The final model performance was assessed by the c-index whereas model's calibration and optimism-corrected c-index were evaluated after 10-fold cross-validation. RESULTS: We identified six independent predictors for pericarditis recurrence, that is age, effusion size, platelet count (negative predictors) and reduced inferior vena cava collapse, in-hospital use of corticosteroids and heart rate (positive predictors). The final model had good performance for recurrence, c-index 0.783 (95% CI 0.725-0.842), while the optimism-corrected c-index after cross-validation was 0.752. Based on these variables, we developed a risk score point system for recurrence (0-22 points) with equally good performance (c-index 0.740, 95% CI 0.677-0.803). Patients with a low score (0-7 points) had 21.3% risk for recurrence, while those with high score (≥12 points) had a 69.8% risk for recurrence. The score was predictive of recurrence among most patient subgroups. CONCLUSIONS: A simple risk score point system based on 6 variables can be used to predict the individualized risk for pericarditis recurrence among patients with a first episode of acute pericarditis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Glucocorticoides/uso terapêutico , Pericardiocentese , Pericardite/terapia , Adulto , Fatores Etários , Idoso , Aspirina/uso terapêutico , Dor no Peito/fisiopatologia , Colchicina/uso terapêutico , Feminino , Febre/fisiopatologia , Frequência Cardíaca/fisiologia , Humanos , Ibuprofeno/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pericardite/sangue , Pericardite/fisiopatologia , Contagem de Plaquetas , Recidiva , Medição de Risco , Fatores de Risco
17.
Elife ; 102021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33944778

RESUMO

Importing necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAAs) are essential amino acids needed for anabolic processes, but they are also imported into the mitochondria for catabolic reactions. What controls the distinct subcellular BCAA utilization during stress adaptation is insufficiently understood. The present study reports the role of SLC25A44, a recently identified mitochondrial BCAA carrier (MBC), in the regulation of mitochondrial BCAA catabolism and adaptive response to fever in rodents. We found that mitochondrial BCAA oxidation in brown adipose tissue (BAT) is significantly enhanced during fever in response to the pyrogenic mediator prostaglandin E2 (PGE2) and psychological stress in mice and rats. Genetic deletion of MBC in a BAT-specific manner blunts mitochondrial BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2 administration. At a cellular level, MBC is required for mitochondrial BCAA deamination as well as the synthesis of mitochondrial amino acids and TCA intermediates. Together, these results illuminate the role of MBC as a determinant of metabolic flexibility to mitochondrial BCAA catabolism and optimal febrile responses. This study also offers an opportunity to control fever by rewiring the subcellular BCAA fate.


Assuntos
Tecido Adiposo Marrom/fisiologia , Aminoácidos de Cadeia Ramificada/metabolismo , Febre/fisiopatologia , Proteínas Mitocondriais/metabolismo , Termogênese/genética , Adaptação Fisiológica , Aminoácidos de Cadeia Ramificada/genética , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias , Proteínas Mitocondriais/genética , Ratos
18.
Proc Natl Acad Sci U S A ; 118(20)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33972431

RESUMO

Febrile seizures (FSs) are the most common convulsion in infancy and childhood. Considering the limitations of current treatments, it is important to examine the mechanistic cause of FSs. Prompted by a genome-wide association study identifying TMEM16C (also known as ANO3) as a risk factor of FSs, we showed previously that loss of TMEM16C function causes hippocampal neuronal hyperexcitability [Feenstra et al., Nat. Genet. 46, 1274-1282 (2014)]. Our previous study further revealed a reduction in the number of warm-sensitive neurons that increase their action potential firing rate with rising temperature of the brain region harboring these hypothalamic neurons. Whereas central neuronal hyperexcitability has been implicated in FSs, it is unclear whether the maximal temperature reached during fever or the rate of body temperature rise affects FSs. Here we report that mutant rodent pups with TMEM16C eliminated from all or a subset of their central neurons serve as FS models with deficient thermoregulation. Tmem16c knockout (KO) rat pups at postnatal day 10 (P10) are more susceptible to hyperthermia-induced seizures. Moreover, they display a more rapid rise of body temperature upon heat exposure. In addition, conditional knockout (cKO) mouse pups (P11) with TMEM16C deletion from the brain display greater susceptibility of hyperthermia-induced seizures as well as deficiency in thermoregulation. We also found similar phenotypes in P11 cKO mouse pups with TMEM16C deletion from Ptgds-expressing cells, including temperature-sensitive neurons in the preoptic area (POA) of the anterior hypothalamus, the brain region that controls body temperature. These findings suggest that homeostatic thermoregulation plays an important role in FSs.


Assuntos
Regulação da Temperatura Corporal/genética , Canais de Cloreto/genética , Febre/genética , Hipertermia/genética , Área Pré-Óptica/metabolismo , Convulsões Febris/genética , Potenciais de Ação/fisiologia , Animais , Animais Recém-Nascidos , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Canais de Cloreto/deficiência , Feminino , Febre/induzido quimicamente , Febre/metabolismo , Febre/fisiopatologia , Expressão Gênica , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Hipertermia/metabolismo , Hipertermia/fisiopatologia , Ácido Caínico/administração & dosagem , Masculino , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Neurônios/patologia , Área Pré-Óptica/fisiopatologia , Isoformas de Proteínas/deficiência , Isoformas de Proteínas/genética , Ratos , Convulsões Febris/induzido quimicamente , Convulsões Febris/metabolismo , Convulsões Febris/fisiopatologia
19.
Sci Rep ; 11(1): 8162, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33854198

RESUMO

Coronary artery abnormalities (CAAs) are a severe complication of Kawasaki disease (KD) that may lead to cardiovascular events. Given the evidence that brachial artery flow-mediated dilation (FMD) decreases in children after the onset of KD, we hypothesized that it could be an early marker of CAA development in the acute stage and investigated its relationship with variation in the coronary artery diameter. A total of 326 sex- and age-matched children were enrolled, including 120 with KD, 109 febrile children and 97 healthy controls. In this study, FMD was significantly decreased in the KD group compared with the febrile and healthy groups. FMD was lower in the CAA group than in the no coronary artery abnormality group. The comparison of FMD showed an obvious difference among the CAA subgroups. The FMD in the coronary aneurysm (CA) group showed a strong negative correlation with the pretreatment maximum coronary artery Z-score (preZmax). While preZmax was 2.5, the receiver operating characteristic curve indicated an optimal cutoff point of 3.44% for FMD. FMD ≤ 3.44% could be considered as a signal of coronary lesions in acute stage of KD.


Assuntos
Artéria Braquial/fisiopatologia , Doença da Artéria Coronariana/diagnóstico , Febre/fisiopatologia , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Adolescente , Circulação Sanguínea , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC
20.
Saudi Med J ; 42(4): 391-398, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33795494

RESUMO

OBJECTIVES: To determine the demographic and clinical characteristics, underlying comorbidities, and outcomes of children with coronavirus disease 2019 (COVID-19) infection. METHODS: In this retrospective study, we reported 62 pediatric patients (age <14 years) with confirmed COVID-19 between March 2 and July 1, 2020, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. RESULTS: Comorbid conditions, including cardiac, neurological, respiratory, and malignant disorders, were reported in 9 patients (14.5%). The most prominent presenting complaints were fever (80.6%) and cough (48.4%). Most of our patients (80.6%) had mild disease, 11.3% had moderate disease, and 8.1% exhibited severe and critical illness. Twenty-one patients (33.9%) were hospitalized, with 4 patients (6.5%) admitted to the pediatric intensive care unit, and 3 (4.8%) patients died. CONCLUSION: All pediatric age groups are susceptible to COVID-19, with no gender difference. COVID-19 infection may result in critical illness and even mortality in subsets of pediatric patients.


Assuntos
COVID-19/fisiopatologia , Dor Abdominal/fisiopatologia , Adolescente , Asma/epidemiologia , Atrofia , Encéfalo/patologia , Bronquiolite Obliterante/epidemiologia , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/terapia , Criança , Pré-Escolar , Comorbidade , Tosse/fisiopatologia , Diarreia/fisiopatologia , Dispneia/fisiopatologia , Feminino , Febre/fisiopatologia , Cardiopatias Congênitas/epidemiologia , Mortalidade Hospitalar , Hospitalização , Humanos , Hidrocefalia/epidemiologia , Lactente , Unidades de Terapia Intensiva Pediátrica , Masculino , Faringite/fisiopatologia , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Rinorreia/fisiopatologia , SARS-CoV-2 , Arábia Saudita/epidemiologia , Índice de Gravidade de Doença , Vômito/fisiopatologia
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